Comparison of the extent to which total hip and total knee arthroplasty restore patient-reported physical function.

OBJECTIVE: To evaluate the extent to which elective total hip arthroplasty (THA) and total knee arthroplasty (TKA) for osteoarthritis (OA) restore normal patient-reported physical function in men and women. METHODS: Pain and physical function (WOMAC-PF) were prospectively measured pre- and post-operatively. The relationship between surgical procedure and achieving physical function equivalent to age and sex-matched adults with no hip or knee joint problems was modeled using sex-specific logistic regression. Percent change in function was also compared between groups using sex-specific generalized linear models adjusted for age, BMI, pain, comorbid conditions, time from surgery, and subsequent surgery. RESULTS: Individuals with pre- and post-operative WOMAC data were classified exclusively into either THA (287M:306F) or TKA (239M:424F) groups. The median follow-up was 476 (THA) and 474 (TKA) days for men, and 495 (THA) and 526 (TKA) days for women. MAIN OUTCOME: women with THA compared with TKA were more likely to achieve a normal level of postoperative PF while there were no significant differences between procedures in men. Additional analyses: we found slightly lower preoperative PF in THA compared with TKA. This difference resolved postoperatively in men, but women who underwent THA reported greater improvement and better PF than those who had TKA. CONCLUSION: In women, THA results in greater improvement in WOMAC-PF at approximately 1-year follow-up and better approximates physical function of community-dwelling older adults without OA than TKA does. In contrast, in men, a lack of between-group post-operative WOMAC-PF differences suggests that procedures result in a similar degree of improvement.

Muscle strength, physical performance and physical activity as predictors of future knee replacement: a prospective cohort study.

OBJECTIVE: To investigate associations between lower levels of muscle strength, physical performance and physical activity and the risk of knee replacement (KR) in older adults with frequent knee pain. METHOD: Participants from the Multicenter Osteoarthritis Study (MOST) with knee pain on most of the past 30 days at baseline were included (n = 1257; mean (SD) age of 62.2 (8.2)). We examined the association between (1) baseline peak isokinetic knee extensor strength, (60°/sec, maximum out of four trials), (2) best time to stand in timed chair stand (2 trials of five repetitions), and (3) baseline Physical Activity Scale for the Elderly score (PASE) with incident KR between baseline and the 84-month follow-up. RESULTS: 1252 (99.6%) participants (1682 knees) completed the follow-up visits. 331 participants (394 knees) underwent a KR during the 84 months (229 women and 102 men). The crude analysis demonstrated a decreased risk of KR in women (P < 0.0001) with higher knee extensor strength (Hazard Ratio (HR; 95% CI) 0.99 (0.98-0.99)). The risk remained significant (P = 0.03) when adjusting for age, BMI, race, clinic site, education, occupation, previous knee injury, previous knee surgery, and WOMAC pain (HR (95% CI) 0.99 (0.99-1.00)), but not when adjusting for Kellgren-Lawrence grade (P = 0.97). CONCLUSION: Lower levels of chair stand performance and self-reported physical activity are not associated with an increased risk of KR within 7 years, while the independent effect of knee extensor strength on risk for KR in women is non-significant after adjusting for radiographic severity.

Changes in patellofemoral and tibiofemoral joint cartilage damage and bone marrow lesions over 7 years: the Multicenter Osteoarthritis Study.

OBJECTIVES: To investigate changes in cartilage damage and bone marrow lesions (BMLs) on MRI in the patellofemoral and tibiofemoral joints (TFJs) over 7 years. METHODS: The Multicenter Osteoarthritis (MOST) Study is a cohort study of persons aged 50-79 years at baseline with or at high risk for knee osteoarthritis (OA). Knees were eligible for the current study if they had knee MRI (1.0T) assessed for cartilage damage and BMLs at the baseline and 84-month visits. Knees were categorized as having MRI-detected structural damage (cartilage and BMLs) isolated to the patellofemoral joint (PFJ), isolated to the TFJ, mixed or no damage at baseline and 84-months. We determined the changes in PFJ and TFJ structural damage over 7 years and used logistic regression to assess the relation of baseline compartment distribution to incident isolated PFJ, isolated TFJ and mixed damage. RESULTS: Among 339 knees that had full-thickness cartilage loss isolated to the PFJ or TFJ at baseline, only 68 (20.1%) developed full-thickness cartilage loss in the other compartment while 271 (79.9%) continued to only have the initial compartment affected. Compared to knees without full-thickness cartilage damage (n = 582), those with isolated TFJ and PFJ full-thickness cartilage damage had 2.7 (1.5, 4.9) and 5.8 (3.6, 9.6) times the odds of incident mixed full-thickness cartilage damage, respectively. Similar results were seen when using other definitions of MRI-defined structural damage. CONCLUSIONS: Most knees with structural damage at baseline do not develop it in the other compartment. Knees that develop mixed structural damage are more likely to start with it isolated to the PFJ.

The relationship between quadriceps muscle weakness and worsening of knee pain in the MOST cohort: a 5-year longitudinal study.

OBJECTIVE: To determine whether quadriceps weakness is associated with elevated risk of worsening knee pain over 5 years. METHODS: The Multicenter Osteoarthritis Study (MOST) is a longitudinal study of 50-79-year-old adults with knee osteoarthritis (OA) or known risk factors for knee OA. The predictor variable was baseline isokinetic quadriceps strength. Covariates included baseline body mass index (BMI), physical activity level, and history of knee surgery. The outcome was worsening pain reported on the Western Ontario and McMaster Universities (WOMAC) Osteoarthritis Index pain subscale or knee replacement surgery between baseline and 5-year follow-up. Analyses were knee-based and used generalized estimating equations, stratified by sex to assess whether the lowest compared with the highest tertile of baseline quadriceps strength was associated with an increased risk of worsening knee pain at 5-year follow-up, controlling for age, BMI, history of knee surgery, and physical activity level as well as correlation between knees within participants. RESULTS: Analyses of worsening knee pain included 4,648 knees from 2,404 participants (61% female). Men with lower quadriceps strength did not have a higher risk of worsening knee pain (RR {95% CI} = 1.01 {0.78-1.32}, P = 0.9183). However, women in the lowest compared with the highest strength tertile had a 28% increased risk of worsening knee pain (RR {95% CI} = 1.28 {1.08-1.52}, P = 0.0052). CONCLUSION: Quadriceps weakness was associated with an increased risk of worsening of knee pain over 5 years in women, but not in men.

The longitudinal relationship between thigh muscle mass and the development of knee osteoarthritis.

OBJECTIVE: Greater quadriceps strength has been found to reduce risk for symptomatic knee osteoarthritis (SxKOA) and knee joint space narrowing (JSN). However, this finding could relate to muscle mass or activation pattern. The purpose of this study was to assess whether greater thigh muscle mass protects against (1) incident radiographic (RKOA), (2) incident SxKOA or (3) worsening of knee JSN by 30-month follow-up. DESIGN: Multicenter Osteoarthritis (MOST) study participants, who underwent dual-energy X-ray absorptiometry (DXA) at the Iowa site were included. Thigh muscle mass was calculated from DXA image sub-regions. Sex-stratified, knee-based analyses controlled for incomplete independence between limbs within subjects. The effect of thigh lean mass and specific strength as predictors of ipsilateral RKOA, SxKOA and worsening of JSN were assessed, while controlling for age, body mass index (BMI), and history of knee surgery. RESULTS: A total of 519 men (948 knees) and 784 women (1453 knees) were included. Mean age and BMI were 62 years and 30 kg/m(2). Thigh muscle mass was not associated with risk for RKOA, SxKOA or knee JSN. However, in comparison with the lowest tertile, those in the highest and middle tertiles of knee extensor specific strength had a lower risk for SxKOA and JSN [odds ratio (OR) 0.29-0.68]. CONCLUSIONS: Thigh muscle mass does not appear to confer protection against incident or worsening knee OA. These findings suggest that future studies of risk for knee OA should focus on the roles of knee extensor neuromuscular activation and muscle physiology, rather than the muscle mass.

Knee malalignment is associated with an increased risk for incident and enlarging bone marrow lesions in the more loaded compartments: the MOST study.

OBJECTIVE: To examine the relationship of knee malalignment with occurrence of incident and enlarging bone marrow lesions (BMLs) and regression of BMLs. METHODS: Subjects from the Multicenter Osteoarthritis Study aged 50-79 years with or at high risk of knee osteoarthritis were studied. Full-limb radiographs were taken at baseline and hip-knee-ankle mechanical axis was measured. Baseline and 30-month magnetic resonance imaging (MRI) of knees (n = 1782) were semiquantitatively assessed for BMLs. Outcome was defined as a change in BML score in femoral/tibial condyle in medial/lateral compartments. Medial compartment in varus alignment and lateral compartment in valgus alignment were combined to form 'more loaded' compartment, while lateral compartment in valgus and medial compartment in varus were combined to form 'less loaded' compartment. Relative risk (RR) of BML score increase or decrease in relation to malalignment was estimated using a log linear regression model with the Poisson assumption, adjusting for age, gender, body mass index, physical activity scale for the elderly, race and clinic site. Further, results were stratified by ipsilateral meniscal and cartilage status at baseline. RESULTS: Baseline varus alignment was associated with higher risk of BML score increase from baseline to follow-up in the medial compartment [adjusted RRs (95%CI): 1.5 (1.2-1.9)] and valgus alignment in the lateral compartment [1.4 (1.0-2.1)]. Increase in BML score was more likely in the more loaded compartments [1.7 (1.4-2.0)] in malaligned knees. Regardless of ipsilateral cartilage or meniscus status, adjusted RR for BML score increase was higher in the more loaded compartments of malaligned knees than those with neutral alignment. Decrease in BML score was less likely in the more loaded compartments in malaligned knees [0.8 (0.7-1.0)]. CONCLUSION: Knee malalignment is associated with increased risk of incident and enlarging BMLs in the more loaded compartments of the tibiofemoral joint.

Elevated tibiofemoral articular contact stress predicts risk for bone marrow lesions and cartilage damage at 30 months.

OBJECTIVE: As cartilage loss and bone marrow lesions (BMLs) are associated with knee joint pain and structural worsening, this study assessed whether non-invasive estimates of articular contact stress may longitudinally predict risk for worsening of knee cartilage morphology and BMLs. DESIGN: This was a longitudinal cohort study of adults aged 50-79 years with risk factors for knee osteoarthritis. Baseline and follow-up measures included whole-organ magnetic resonance imaging score (WORMS) classification of knee cartilage morphology and BMLs. Tibiofemoral geometry was manually segmented on baseline magnetic resonance imaging (MRI), and three-dimensional (3D) tibiofemoral point clouds were registered into subject-specific loaded apposition using fixed-flexion knee radiographs. Discrete element analysis (DEA) was used to estimate mean and peak contact stresses for the medial and lateral compartments. The association of baseline contact stress with worsening cartilage and BMLs in the same subregion over 30 months was assessed using conditional logistic regression. RESULTS: Subjects (N = 38, 60.5% female) had a mean ± standard deviation (SD) age and body mass index (BMI) of 63.5 ± 8.4 years and 30.5 ± 3.7 kg/m2 respectively. Elevated mean articular contact stress at baseline was associated with worsening cartilage morphology and worsening BMLs by 30 months, with odds ratio (OR) [95% confidence interval (CI)] of 4.0 (2.5, 6.4) and 6.6 (2.7, 16.5) respectively. Peak contact stress also was significantly associated with worsening cartilage morphology and BMLs {1.9 (1.5, 2.3) and 2.3 (1.5, 3.6)}(all P < 0.0001). CONCLUSIONS: Detection of higher contact stress 30 months prior to structural worsening suggests an etiological role for mechanical loading. Estimation of articular contact stress with DEA is an efficient and accurate means of predicting subregion-specific knee joint worsening and may be useful in guiding prognosis and treatment.

Quadriceps weakness predicts risk for knee joint space narrowing in women in the MOST cohort.

OBJECTIVE: Quadriceps weakness has been reported with incident but not progressive knee osteoarthritis (OA) in longitudinal studies. This study examined the relationship between quadriceps strength and worsening of knee joint space narrowing (JSN) over 30 months. METHODS: Longitudinal, observational study of adults aged 50-79 years with OARSI JSN score <3 at baseline. Baseline measures included bilateral weight-bearing fixed flexion radiographs, isokinetic concentric quadriceps and hamstring strength, height and weight, and physical activity. Hamstring:quadriceps (H:Q) strength ratios also were evaluated. Worsening was defined as an increase in JSN score in the tibiofemoral and/or patellofemoral compartments on 30-month radiographs or total knee replacement. Knee-based analyses used generalized estimating equations, stratified by sex, to assess relationships between strength and knee JSN while controlling for covariance between knees within subjects as well as age, body mass index (BMI), history of knee injury and/or surgery, physical activity level and alignment. RESULTS: 3856 knees (2254 females and 1602 males) with JSN score <3 at baseline and no missing follow-up data were included. Mean+/-SD age was 62.2+/-7.7 in women and 61.6+/-8.1 in men. Women in the lowest tertile of quadriceps strength had an increased risk of whole knee JSN (OR=1.66, 95% CI=1.26, 2.19) and tibiofemoral JSN (OR=1.69, 95% CI=1.26, 2.28). However, no associations were found between strength and JSN in men or H:Q<0.6 and JSN in men or women. CONCLUSIONS: In women but not in men, quadriceps weakness was associated with increased risk for tibiofemoral and whole knee JSN.

Occipital horn syndrome and a mild Menkes phenotype associated with splice site mutations at the MNK locus.

We have found mutations in the Menkes disease gene (MNK) which impair, but do not abolish, correct mRNA splicing in patients with less severe clinical phenotypes. In one family, four males aged 2-36 years with a distinctive Menkes variant have a mutation at the +3 position of a splice donor site near the 3' end of the Menkes coding sequence that is associated with exon skipping and a stable mutant transcript. In an unrelated 15-year-old male with typical occipital horn syndrome, a point mutation at the -2 exonic position of a splice donor site in the middle of the gene causes exon-skipping and activation of a cryptic splice acceptor site. In both mutations, maintenance of some normal splicing is demonstrable by RT-PCR, cDNA sequencing and ribonuclease protection.